Lu Yi-Chin, Tseng Liang-Wei, Wu Chiao-En, Yang Ching-Wei, Yang Tsung-Hsien, Chen Hsing-Yu
Division of Chinese Internal Medicine, Center for Traditional Chinese Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Division of Chinese Acupuncture and Traumatology, Center of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Front Pharmacol. 2024 May 24;15:1364318. doi: 10.3389/fphar.2024.1364318. eCollection 2024.
BACKGROUND: Esophageal cancer (EC) is a major cause of cancer-related mortality in Taiwan and globally. Patients with EC are highly prone to malnutrition, which adversely affects their prognosis. While Chinese herbal medicine (CHM) is commonly used alongside conventional anti-cancer treatments, its long-term impact on EC patients with malnutrition remains unclear. METHODS: This study utilized a multi-center cohort from the Chang Gung Research Database, focusing on the long-term outcomes of CHM in EC patients with malnutrition between 1 January 2001, and 31 December 2018. Patients were monitored for up to 5 years or until death. Overall survival (OS) rates were calculated using the Kaplan-Meier method. Overlap weighting and landmark analysis were employed to address confounding and immortal time biases. Additionally, the study analyzed prescription data using a CHM network to identify key CHMs for EC with malnutrition, and potential molecular pathways were investigated using the Reactome database. RESULTS: EC patients with malnutrition who used CHM had a higher 5-year OS compared with nonusers (22.5% vs. 9% without overlap weighting; 24.3% vs. 13.3% with overlap weighting; log-rank test: = 0.006 and 0.016, respectively). The median OS of CHM users was significantly longer than that of nonusers (19.8 vs. 12.9 months, respectively). Hazard ratio (HR) analysis showed a 31% reduction in all-cause mortality risk for CHM users compared with nonusers (HR: 0.69, 95% confidence interval: 0.50-0.94, = 0.019). We also examined 665 prescriptions involving 306 CHM, with Willd. exhibiting the highest frequency of use. A CHM network was created to determine the primary CHMs and their combinations. The identified CHMs were associated with the regulation of immune and metabolic pathways, particularly in areas related to immune modulation, anti-cancer cachexia, promotion of digestion, and anti-tumor activity. CONCLUSION: The results of this study suggest a correlation between CHM use and improved clinical outcomes in EC patients with malnutrition. The analysis identified core CHMs and combinations of formulations that play a crucial role in immunomodulation and metabolic regulation. These findings lay the groundwork for more extensive research on the use of CHM for the management of malnutrition in patients with EC.
背景：食管癌（EC）是台湾地区及全球癌症相关死亡的主要原因。食管癌患者极易出现营养不良，这对其预后产生不利影响。虽然中药（CHM）通常与传统抗癌治疗联合使用，但其对营养不良的食管癌患者的长期影响仍不明确。 方法：本研究利用长庚研究数据库中的多中心队列，重点关注2001年1月1日至2018年12月31日期间营养不良的食管癌患者使用中药的长期结局。对患者进行长达5年的监测或直至死亡。采用Kaplan-Meier方法计算总生存率（OS）。采用重叠加权和地标分析来解决混杂和不朽时间偏倚问题。此外，该研究使用中药网络分析处方数据，以确定治疗营养不良食管癌的关键中药，并使用Reactome数据库研究潜在的分子途径。 结果：使用中药的营养不良食管癌患者的5年总生存率高于未使用者（未进行重叠加权时为22.5%对9%；进行重叠加权时为24.3%对13.3%；对数秩检验：分别为=0.006和0.016）。中药使用者的总生存期中位数显著长于未使用者（分别为19.8个月和12.9个月）。风险比（HR）分析显示，与未使用者相比，中药使用者的全因死亡风险降低了31%（HR：0.69，95%置信区间：0.50-0.94，=0.019）。我们还检查了涉及306种中药的665份处方，其中威灵仙的使用频率最高。构建了一个中药网络以确定主要中药及其组合。所确定的中药与免疫和代谢途径的调节有关，特别是在免疫调节、抗癌恶病质、促进消化和抗肿瘤活性等方面。 结论：本研究结果表明，使用中药与改善营养不良食管癌患者的临床结局之间存在相关性。分析确定了在免疫调节和代谢调节中起关键作用的核心中药及其配方组合。这些发现为更广泛地研究使用中药治疗食管癌患者的营养不良奠定了基础。
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